Menstruation pulls the trigger for inflammation and pain in endometriosis

•Retrograde menstruation and endometriotic lesions release proinflammatory and pro-nociceptive mediators.•Retrograde menstruation is the trigger for inflammation and pain in endometriosis.•Targeting peripheral mechanisms in endometriosis-associated inflammatory pain may lead to improved treatment.•Mechanisms causing inflammatory pain in endometriosis are relevant for other inflammatory disorders.

Endometriosis is a chronic, hormone-dependent, inflammatory disease, characterized by the presence and growth of endometrial tissue outside the uterine cavity. It affects 5–10% of the female population of reproductive age and is frequently associated with moderate to severe pain, subfertility, and a marked reduction in health-related quality of life. Here, we propose a new pathophysiological concept of endometriosis, summarizing recent findings in one unifying picture. We propose menstruating tissue as the trigger for inflammatory pain in endometriosis through the activation of innate immune cells and peripheral nerve endings. We speculate how innovative treatment modalities beyond hormonal treatment will improve patients’ lives.